HSV-tk + Valacyclovir + SBRT + Chemotherapy for Recurrent GBM

NCT03596086 | Recruiting Phase 1 FDA Drug

• 1 other identifier: Pro00016414
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Study to assess the safety and efficacy of HSV-tk (gene therapy), valacyclovir, radiotherapy and chemotherapy in recurrent glioblastoma multiforme.

Conditions

Glioblastoma Multiforme; Astrocytoma, Grade III

Keywords

GBM; glioblastoma; Astrocytoma

Outcome Measures

Primary Outcomes (1)

• Survival in months from Study drug administration (Day 0)

  The overall survival in months of recurrent GBM patients drug administration up to five years

  Up to 60 months as measured in months.

Secondary Outcomes (1)

• Progression Free Survival assessments will be done every 6-8 weeks for 1st year thereafter every 12-14 weeks until disease progression or death

  Up to 60 months as measured in months

Study Arms (1)

ADV/HSV-tk (gene therapy)

EXPERIMENTAL

The gene therapy investigational product, HSV-tk will be injected during the surgery. Within 24 hours valacyclovir will be given for 14 days. Radiotherapy will be administered over 10 sessions (over 2 weeks) starting within 9 days of surgery. Standard of care/routine chemotherapy will be started concurrent or after completion of the radiotherapy dependent on patient status based on best clinical judgment. Patient can receive second treatment of HSV-tk after 6 months

Drug: ADV/HSV-tk (gene therapy)

Interventions

ADV/HSV-tk (gene therapy) DRUG

The investigational adenovirus gene therapy injected at tumor site followed by valacyclovir, radiotherapy, and chemotherapy

Also known as: gene transfer, gene therapy, HSV-tk

ADV/HSV-tk (gene therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have biopsy proven recurrent anaplastic astrocytoma or glioblastoma multiforme without evidence of multifocal tumor or brainstem involvement. Multifocal disease does not exist if enhancing areas are connected by abnormal T2 FLAIR on the MRI scan.
• Radiographic evidence of recurrence/progression by iRANO criteria
• ≥ 3 weeks since any major surgery, completion of RT, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy).
• Life expectancy ≥ 12 weeks.
• Patient can receive second treatment of HSV-tk after 6 months
• Patients should have the following characteristics: recurrent glioblastoma or AA demonstrated by biopsy or imaging study, ECOG performance status of 0-1, has had prior surgery and radiotherapy /chemotherapy for the glioblastoma.
• Patients with leptomeningeal disease may be considered for enrollment into the study.
• No evidence of other active malignancy (except squamous or basal cell skin cancers).
• Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks of the study by the investigator (or his/her designee) with the aid of written information.
• Willing to provide biopsies as required by the study.
• WOCBP must have a negative serum pregnancy test within 7 days prior to the administration of the first study treatment. Women must not be lactating.
• WOCBP and men must practice an effective method of birth control
• Patients must have adequate baseline organ function as assessed by the following laboratory values before initiating the protocol:
• serum creatinine \< 1.5 mg/dL
• T. bilirubin \< 2.5 mg/dL, ALT, AST, GGT and AP \< 2 x normal

You may not qualify if:

• Prior treatment with immunomodulatory therapy, immunotherapy, and/or gene vector therapy in the past 3 months.
• Any cytotoxic chemotherapy, RT, or immunotherapy or any investigational drug for this brain tumor within 3 weeks of study treatment start.
• Evidence of multifocal disease, brainstem involvement
• Patients on immunosuppressive drugs (other than steroids for brain edema).
• In patients with leptomeningeal disease, no evidence of diffuse disease or spread to the spine.
• In patients with leptomeningeal disease, no bulky leptomeningeal metastases with potential to obstruct CSF flow will not be enrolled.
• Liver disease, such as cirrhosis or active/chronic hepatitis B or C.
• History of or current alcohol misuse/abuse within the past 12 months.
• Known or suspected allergy or hypersensitivity to any component of the proposed regimen (gene vector-HSV-tk, Valacyclovir).
• Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications (Valacyclovir).
• No active malignancy except for non-melanoma skin cancer or in situ cervical cancer or treated cancer from which the patient has been continuously disease free for more than 5 years.
• Pregnant or breastfeeding women or women/men able to conceive and unwilling to practice an effective method of birth control. WOCBP must have a negative serum pregnancy test within 7 days prior to the administration of the first study treatment.
• Presence of active or suspected acute or chronic uncontrolled infection or history of immunocompromise, including a positive HIV test result.
• Patients \< 18 years of age
• Unwilling or unable to comply with the study protocol.

Sponsors & Collaborators

• David Baskin MD: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (1)

Houston Methodist Neurological Institute

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Astrocytoma

Interventions

Genetic Therapy; Genetic Engineering

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Genetic Techniques; Investigative Techniques

Study Officials

• David S Baskin, MD

  Houston Methodist Neurological Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David S Baskin, MD

CONTACT

713-441-3803 or 713-201-5792; DBaskin@houstonmethodist.org

Helga M Jones

CONTACT

713-363-9388; HMJones@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Houston Methodist Neurosurgeon and Principal Investigator

Study Record Dates

• First Submitted: March 20, 2018
• First Posted: July 23, 2018
• Study Start: December 11, 2017
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

US (1)